血管生成作为I期非小细胞肺癌手术切除后生存的预测指标。

Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer.

作者信息

Duarte I G, Bufkin B L, Pennington M F, Gal A A, Cohen C, Kosinski A S, Mansour K A, Miller J I

机构信息

Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

J Thorac Cardiovasc Surg. 1998 Mar;115(3):652-8; discussion 658-9. doi: 10.1016/S0022-5223(98)70331-9.

DOI:10.1016/S0022-5223(98)70331-9

PMID:9535454

Abstract

OBJECTIVES

Some patients with surgically resected stage I non-small-cell lung cancer eventually have metastatic disease. A histologic marker of metastatic potential and diminished survival for stage I non-small-cell lung cancer may distinguish this patient population. This study evaluates the degree of angiogenesis as a predictor of cancer-related death after operation for stage I non-small-cell lung cancer.

METHODS

Demographic, surgical, and histopathologic data, including presence of vascular invasion, were reviewed for 106 patients with stage I non-small-cell lung cancer from 1985 through 1990. Visual quantitation of microvessels immunostained with factor VIII-related antigen and CD31 in 5 microm sections from the paraffin blocks of tissue defined rumor angiogenesis.

RESULTS

Follow-up was 95.1% complete, mean 5.2 +/- 3.0 years. Lung cancer-related mortality rate was 24.4% at 5 years. Mean microvessel counts were 20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31. Univariate analysis revealed an FVIII count of at least 20 (p = 0.025) and blood vessel invasion (p = 0.017) to be significant predictors of disease-related death. After adjustment for other patient and tumor characteristics, multivariate Cox regression analysis found an FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (hazard ratio 3.7) to be significant independent correlates of lung cancer death (p = 0.018 and p = 0.011, respectively). CD31 quantitation did not predict survival on univariate or multivariate analyses and did not correlate strongly with FVIII quantitation (Spearman's rank correlation r = 0.19).

CONCLUSIONS

This analysis reveals a significant association between tumor neovascularization and cancer-related mortality rate among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and metastatic potential, may define a subset of patients with stage I non-small-cell lung cancer who could benefit from adjuvant therapy after surgical resection.

摘要

目的

部分接受手术切除的Ⅰ期非小细胞肺癌患者最终会发生转移性疾病。Ⅰ期非小细胞肺癌转移潜能和生存期缩短的组织学标志物可能有助于区分这类患者群体。本研究评估血管生成程度作为Ⅰ期非小细胞肺癌术后癌症相关死亡的预测指标。

方法

回顾了1985年至1990年间106例Ⅰ期非小细胞肺癌患者的人口统计学、手术及组织病理学数据，包括血管侵犯情况。通过对组织石蜡块5微米切片中用VIII因子相关抗原和CD31免疫染色的微血管进行视觉定量来确定肿瘤血管生成情况。

结果

随访完成率为95.1%，平均随访时间为5.2±3.0年。5年时肺癌相关死亡率为24.4%。VIII因子的微血管平均计数为20.7±11.2，CD31的微血管平均计数为29.6±18.1。单因素分析显示，VIII因子计数至少为20（p = 0.025）和血管侵犯（p = 0.017）是疾病相关死亡的显著预测因素。在对其他患者和肿瘤特征进行调整后，多因素Cox回归分析发现，VIII因子计数至少为20（风险比2.9）和血管侵犯（风险比3.7）是肺癌死亡的显著独立相关因素（分别为p = 0.018和p = 0.011）。CD31定量在单因素或多因素分析中均不能预测生存期，且与VIII因子定量的相关性不强（Spearman等级相关r = 0.19）。